The goal of this research proposal is to test the hypothesis that estrogen-induced changes in microglial proteasome subunit expression participate in the anti-inflammatory effects of estrogen. Through these studies, insights will be gained into estrogen-induced microglial modulation and the role that the proteasome plays in microglial inflammatory responses. Modulation of proteasome subunit expression can potentially affect cell surface MHC expression, NF-kB regulation, and cytokine production, and thus may be an important target for future therapeutic intervention. The specific aims for this proposal are: 1) To test the hypothesis that immune stimuli will alter the composition of the proteasome causing immunoproteasome formation in cultured murine and human microglial/macrophages 2) To test the hypothesis that estrogen will prevent changes in proteasome composition induced by immune stimuli 3) To test the hypothesis that prevention of immunoproteasome subunit expression is responsible, at least in part, for the anti-inflammatory effects of estrogen on microglial and macrophage activation. [unreadable] [unreadable]